Effect of Aqueous Extract Withania somnifera on Tolerance to Antiepileptic Effect of Phenobarbitone in Mice

Objective: To evaluate neuroprotective and antioxidant properties in Phenobarbitone (PHB) induced tolerant effect of aqueous extract of withania somnifera (WS) in mice. Materials & Methods: Male Swiss albino mice were screened for hind limb tonic extension (HLTE). Animals were divided into 6 groups, Group 1 and 2 served as controls, which received vehicle and PHB (25 mg/kg, i.p.) respectively. Group 3 received PHB (25 mg/kg, i.p.) and after two hr induced to maximal electric shock (MES) at alternate day for 18 days, incidence of HLTE on two consecutive days taken as endpoint. Group 4, 5 and 6 MES was induced 2 hr following co-administration of PHB (25 mg/kg, i.p.) and WS (500, 750 and 1000 mg/kg p.o. respectively). At the end of 18th day, mice behaviour tests were performed, after those animals were sacrificed by overdosing of anaesthesia and brain were collected for estimation of malondialdehyde (MDA) and reduced glutathione (GSH). Results: After WS treated (500 mg/kg) mice were showed 80% of tolerance effect which has similar to phenobarbitone treated mice. The higher dose treated of WS (750 and 1000 mg/kg) mice were showed maximum at 20% of the tolerance effect in MES induced epilepsy. MDA levels were decreased and GSH levels increased significantly. Higher dose of WS treated mice were showed significant improvement in cognitive functions. Conclusion: These findings suggests that aqueous extract of WS (750, 1000 mg/kg) adjuvant to PHB delay in development of tolerance and added advantage of prevention of cognitive impairment and oxidative stress.